Introduction
Non-alcoholic fatty liver disease (NAFLD) is an initial manifestation of various pathological conditions, such as non-alcoholic steatohepatitis, cirrhosis and, liver malignancies 1. The most implicated mechanism for NAFLD is insulin resistance2. Supra-physiological levels of glucose, sucrose, and, fructose can induce lipogenic genes through various mechanisms that lead to de novo lipogenesis and inhibit fatty acid oxidation causing deposition of fatty acids in various organs such as liver3. Latter combined insulin resistance, hormones secreted by the adipocytes, nutritional factors, gut microbiota and, genetic factors to describe the pathogenesis of NAFLD. The pooled regional incidence of NAFLD in Asian countries is 52 per 1,000 person-years compared to 28 per 1,000 person-years in the West4. The prevalence of lean NAFLD in Asia is 19%, while it is 7% in the United States 5.
While NAFLD is the commonest liver disease in the west, its effect on pregnancy has not been discussed widely until recently6. Early retrospective studies have reported a low prevalence (28.9/100,000 per pregnancies) on NAFLD 7, yet with definitive adverse pregnancy outcomes. Recent studies show a varying degree of NAFLD among pregnant women, with 15% in Canada8, 14.3%-16.7% in USA9,10, 18.4% in Korea 11, and 18.2% in Sri Lanka12. The secondary data analysis of US inpatient sample of 18,574,225 pregnancies shows that the prevalence of NAFLD after 20 weeks of gestation has tripled over a period of 10 years13. Since its first report in 2011, NAFLD is identified as a major predictor of many fetal and maternal adverse outcomes including miscarriages 14, gestational diabetes mellitus (GDM) 11,15–18, hypertensive complications 19,20, higher caesarean sections20, intrahepatic cholestasis in pregnancy21, pre-term birth 19, low birth weight 21 and postpartum haemorrhage7.
Being an insulin-resistant state, pregnancy itself has a higher risk for NAFLD as well as developing hyperglycaemia. Thus, one of the main adverse pregnancy outcomes associated with NAFLD is GDM. The pooled global prevalence of GDM using IADPSG criteria is reported as 10.6% (95% CI 10.5–10.6%) 22 whereas the estimates for 2005-2015 shows a wide disparity across WHO regions ranging from 5.8% in Europe to 12.9 in middle East and north Africa. The incidence of GDM among pregnant women with NAFLD was shown to be more than 20%23. and the severity of NAFLD is proportional to the risk of GDM and large for gestational age (LGA) babies24. The unconfounded effect of NAFLD on GDM was estimated with an odds ratio around two in two prospective cohort studies; one with OR 2.50 (95% CI 1.07, 5.77) 23 and another with an OR 2.2 (95% CI: 1.1–4.3) 25 and 6.5, (95% CI: 2.3–18.5) in another study. While early pregnancy NAFLD is almost established as a major predictor of GDM, only a limited number of prospective studies are available in global literature and none from South Asian region, a region having high incidence of both NAFLD and GDM. According to our knowledge none of prospective studies are available globally about the association between NAFLD and miscarriages. The purpose of the present study was to determine the role of NAFLD as a risk factor for GDM and early pregnancy miscarriages among Sri Lankan pregnant women.